The antigen-induced breakdown of membrane phospholipids appear to be mediated by a Gz-like protein and is associated with an increase in concentration of cytosolic Ca2+ ([Ca2+]i) and exocytosis in RBL-2H3 cells. All these responses were dependent on influx of Ca2+ through a nonselective voltage-independent cation channel that could carry Na+, Ca2+, Mn2+ and Sr2+ but not Zn2+ and La3+. The influx of Ca2+ allowed an increase in [Ca2+li and replenishment of intracellular Ca2+ stores. Influx through this channel was enhanced in cells treated with cholera toxin - which activates a Gs-like G-protein - and suppressed in cells depolarized with high [K+]o. Other studies indicated that adenosine receptors in RBL-2H3 cells are coupled to the inositol phospholipid-specific phospholipase C via a G-protein that is inhibited by both pertussis toxin and cholera toxin. In addition, ADP-ribosylation studies revealed the presence of cytosolic protein (kDa, 97) as a substrate for endogenous ADP-ribosylating activity. This activity is enhanced by adenosine receptor stimulation. As reported elsewhere (see report Z01 00990 04 LCP) the responses of antigen are selectively down regulated and those to adenosine up regulated in dexamethasone-treated cells. Mapping of mRNA for G-proteins in these cells revealed the expected array of G-proteins and a decrease of mRNA for Gza in dexamethasone treated cells, to indicate that this is the most likely G-protein coupled to the IgE receptor and phospholipase C. The studies in total indicated the recruitment of several G-proteins in activate RBL-2H3 cells which in turn activated various phospholipases, ion channels and possibly some other mechanisms to provide the necessary signals for secretion by these cells.